Charles Roberts
The twin epidemics of obesity and diabetes are overwhelming healthcare systems worldwide, and these conditions create an increased risk for heart disease, cancer, and mental disorders. Improved diagnostic tests and therapies to detect and treat obesity, diabetes, and their complications requires the use of model systems that are relevant to human disease. These include human cell systems and complementary non-human primate models that are more likely to predict efficacy in human patients.
Specific research projects:
The Roberts laboratory has a long-term focus on various aspects of the insulin-like growth factor signaling system, which has crucial roles in mammalian growth and development, metabolic control, and tumorigenesis. Three specific areas currently under investigation are:
Regulation of insulin action by insulin-like growth factors. We have recently shown that IGF-I can act through the insulin receptor in addition to its own classical receptor, the IGF-I receptor. This cross-talk is consistent with the idea that IGF-I is an intrinsic co-ligand for the insulin receptor, and that IGF-I and IGF-II analogs may represent novel compounds for diabetes therapy.
HER/erbB-IGF-I receptor interactions. We have shown that a novel product of the HER-2 proto-oncogene, termed herstatin, inhibits both EGFR family and IGF-I receptor action and represents a unique, bi-functional inhibitor of growth factor signaling relevant to breast, prostate, and other cancers. We are designing alternative versions of herstatin that can serve as promising protein therapeutics for cancer treatment.
Ex vivo islet culture. We are developing novel methods for maintenance of isolated primate islets, including physiological O2levels and 3-D culture to assess the efficacy of IGFs and other factors on islet function. These approaches will facilitate the evaluation of current and emerging diabetes therapies for their islet-autonomous effects.
Biography
Charles Roberts is Associate Director for Translational Research and Development and Senior Scientist in the Divisions of Neuroscience and Reproductive Sciences at the Center, and Professor of Medicine, Pediatrics, and Cell and Developmental Biology at OHSU. He received his Ph.D. in biochemistry and molecular biology at the University of California, Santa Barbara (UCSB), in 1975. Following an American Cancer Society-supported postdoctoral fellowship, he was an Assistant Professor of Biological Sciences at UCSB from 1978-1984. He was then recruited to the Diabetes Branch at the National Institutes of Health in 1984 as a Special Expert, was appointed Associate Chief of the Section of Molecular Physiology in 1989 with tenure, and promoted to Senior Investigator in 1992. In 1994, Dr. Roberts came to OHSU as Professor of Pediatrics and Associate Chair for Research. He moved to the Center in 2007.
Recent Publications
Denley, A., Brierley, G.V., Carroll, J.M., Lindenberg, A., Booker G.W., Cosgrove, L.J., Wallace, J.C., Forbes, B.E., and Roberts, C.T., Jr. Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain. Endocrinology 147:1029-1036 (2006).
Rose, P.P., Carroll, J.M., Carroll, P.A., DeFilippis, V.R., Lagunoff, M., Moses, A.V., Roberts, C.T., Jr., and Frueh, K.The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's Sarcoma. Oncogene 26:1995-2005 (2007).
Denley, A., Carroll, J.M., Brierley, G.V., Cosgrove, L., Wallace, J.C., Forbes, B.E., and Roberts, C.T., Jr. Differential activation of insulin receptor substrates (IRS)-1 and 2 by IGF-activated insulin receptors. Mol. Cell. Biol. 27:3569-3577 (2007).
